Treatment of tumors, including cancers, is an area of clinical medicine that remains fraught with complications and often presents an array of suboptimal treatment choices. A major problem in treating cancer is that most or all of the known therapies have serious adverse side effects. For example, surgery is commonly employed to remove a cancer from a patient. However, surgery often disfigures the patient or interferes with normal bodily functions. Other treatments such as chemotherapy and radiation treatment also cause undesired side effects.
Kaposi's sarcoma (KS) is one example of a cancer that is difficult to treat. Kaposi's sarcoma is the most common malignancy in patients with acquired immunodeficiency syndrome (AIDS) in the United States. KS occurs in approximately 30% of male AIDS patients, but only 3% of female AIDS patients Elford et al. (1991) AIDS 7: 1667-1671!. The exact mechanism by which KS develops is unknown. Kaposi's sarcoma is a multifocal neoplasm, consisting of several cell types and abundant angiogenesis. The tumor cell is believed to be a spindle-shaped cell and is usually considered to be of endothelial origin Rutgers et al. (1986) Am. J. Pathol. 122: 493-499!. However, its precise cellular origin and even its classification as a true monoclonal malignancy versus a polyclonal hyperplasia have remained elusive Shaw et al. (1984) Science 226: 1165-1171; Holden et al. (1989) J. Invest. Dermatol. 93: 119S-124S; Hashimoto et al. (1987) Pathol. Res. Pract. 182: 658-668!.
Existing Kaposi's sarcoma treatments often cause myelotoxicity and neurotoxicity see, e.g. Northfeldt et al. (1991) Hematology/Oncology Clinics of North America 5: 297-310, which is incorporated herein by reference!. Presently available Kaposi's sarcoma therapies can also induce immunosuppression, compounding the pre-existing immunodeficiency that is usually present in AIDS patients.
Thus, a great need exists for a treatment for Kaposi's sarcoma and other cancers that does not cause severe adverse side effects. Hormonal treatments offer promise of such a treatment.
Many cancers secrete hormones such as human chorionic gonadotropin (hCG) and/or an hCG subunit. Indeed, elevated hCG serum concentration is considered a reliable indicator of the presence of some tumors see, e.g., Bagshawe (1992) Acta Oncol. 31: 99-106; Stenman et al. (1993) Scand, J. Clin. Lab. Invest. Suppl. 216: 42-78; Mann et al. (1993) Scand. J. Clin. Lab. Invest. Suppl. 216: 97-104!. Elevated serum levels of hCG or an hCG subunit are found in patients having gestational trophoblastic tumors and testicular germ cell tumors, as well as nongonadal and nontrophoblastic tumors such as cancers of the bladder, pancreas, cervix, lung, liver, and stomach Bidart et al. (1993) TEM 4: 285-291; Marcillac et al. (1992) Cancer Res. 52: 3901-3907; Alfthan et al. (1992) Cancer Res. 52: 4628-4633!.
Human chorionic gonadotropin belongs to a family of glycoprotein hormones, human luteinizing hormone (lutropin, hLH), follitropin (FSH), and thyrotropin (TSH). Each of these hormones is composed of two dissimilar, noncovalently bound subunits, .alpha. and .beta.. The hormones share a common .alpha. subunit, while the .beta. subunits differ slightly in length and amino acid sequence Ryan et al. (1988) FASEB J. 2:2661-2669; Ward et al. in Reproduction in Domestic Animals, 4th ed., Cuppos, PT, ed., pp. 25-80, Academic Press, N.Y. (1991)!. The most closely related of the .beta. subunits are those of hCG and hLH, which are 85% identical, except for an approximately 20 amino acid extension on the carboxy terminus of hCG. Indeed, hCG and hLH act through a common receptor Loosfelt et al. (1989) Science 245:525-528; McFarland et al. (1989) Science 245:494-499! and elicit identical biological responses Pierce and Parsons (1981) Ann. Rev, Biochem. 50:466; Strickland et al. in Luteinizing hormone action and receptors, M. Ascoli, Ed., CRC Press, Boca Raton Fla., 1985, p. 1!
The present invention is based on the discovery that hCG and related hormones are useful not only as a marker for detecting cancers, but also as a treatment for cancers. Provided herein are an effective methods for treating cancers using human hormones such as human chorionic gonadotropin or human lutropin, and articles of manufacture that are useful for carrying out these methods.